Audit of warfarin reversal in over-anticoagulated patients

D Wright and J Seal

Department of Haematology

Pontefract General Infirmary

Nov 2002

Bleeding during warfarin therapyRisk factors

• Age

• High target INR

• Actual INR

• PMH of bleeding

• CVA

• Hypertension

• Alcohol/liver disease

Risk of bleeding whilst on warfarin

ISCOAT study

Prospective study of 2745 patients

Bleeding complications: All 7.6 per 100 patient years

Major 1.1 per 100 patient years

Fatal cerebral bleeds 0.25 per 100 patient years

Age > 70 : 10.5 per 100 patient years

< 70 : 6 per 100 patient years

Risk of bleeding whilst on oral anticoagulation

INR Bleeding events per 100 patient years

2 – 3 4.8

3 – 4.5 9.5

4.5 – 7 40.5

>7 200

ISCOAT study: Lancet 1996

Aim of study

• Establish a baseline audit of historical practice of warfarin omission in patients with INR>8

• Assess feasibility of using oral vitamin K to reverse anticoagulation in patients with INR>8

Methods• Patients attend community phlebotomy

clinics for venous blood sampling.

• At this visit patient completes a record sheet detailing warfarin dose, change in medication, clinical condition and any bleeding symptoms.

• Samples are sent to central lab for INR testing, along with record sheet. Results are downloaded to A/C computer. BMS reviews results.

INR Advice Given5.5 - 7.0 Inclusive Miss 3 days.Repeat INR

In 1 week. Reduce Dose

7.1 - 8.0 Inclusive Miss 3 days. Repeat INR in 3 days. No dose given. See High INR policy.

8.1 and above Unable to calculate dose

See High INR policy

INR OVER 8.0

• Significant bleeding symptoms – refer to A/E

• No Bleeding – inform Clinical Haematologist

• Give 2mg oral dose Vitamin K (KONAKION)

• See separate SOP for prescription

• Warfarin discontinued temporarily

INR OVER 8.0

• Arrange for INR next day. Repeat INR daily until INR <6.0

• If INR remains over 8.0 repeat Vitamin K

• If patient unable to receive Vitamin K discontinue for 3 days and re-check INR

• Complete a case report

• Send a fax to inform GP

INR 7.1 – 8.0

• Significant bleeding symptoms – refer to A/E

• No bleeding proceed as follows

• Stop Warfarin for 3 days and re-check INR

• Advise patient to attend A/E if bleeding develops

INR 7.1 – 8.0

• Send a fax to inform GP

• Recommence warfarin when INR is back in the therapeutic range

• Complete a case report

CASE REPORT FOR OUT PATIENTS WITH HIGH INR’S OVER 7.0

SURNAMESeal

DOB16/01/1949

GPDr Waring

FORENAMEJohn

HOSPITAL NO.1234567

TARGET INR2.5

AC REASONAF

MAINTENANCE DOSE5.0mg

CAUSE OF OVER-ANTICOAGULATIONAlcohol

Warfarin start date: 15/07/2001…………………….

Other recent medication:Amoxyxcillin……………………………………..

DATE INR 2MGVITAMIN K

GIVEN

FAXTOGP

WARFARINDOSE

PRESCRIBED

SYMPTOMS

DAY 1 01/11/02 9.9 Nil None

DAY 2 02/11/02 4.7 Nil

DAY 3 Nil

DAY 4 4mg daily

DAY 5

DAY 6

FollowUp

07/11/02 2.7 4mg daily

Patient Outcome:Back in range off alcohol………………………………….

Restarting Warfarin

• If over anticoagulation is clearly secondary to a transient event, which has now resolved, then restart Warfarin at the previous maintenance dose

• If the reason for over anticoagulation is unknown or due to a continuing risk factor, then restart at a dose between 20% and 25% less than the previous maintenance dose

Results

• Between Feb - Dec 2001 forty-one patients had an INR>8 in the absence of significant bleeding

• 20 received oral vitamin K

• 21 were managed by Warfarin omission

Vitamin K (n=20)

Warfarin omission (n=21)

Age: Mean 68 67

Range 34-86 36-94

Duration of therapy:

Median 4.8yrs 5yrs

Range 0.1-19 1-16

Baseline INR:

Mean 12.8 10.2

Range 8.7-22.5 8.1-19.9

Characteristics of high INR patients

Vitamin K Warfarin omission

AF 8 12

DVT/PE 6 4

Mechanical valve

3 5

PVD 3 0

Indications for warfarin therapy

Causes of over-anticoagulation

Vitamin K group (n=20)

Warfarin omission

group (n=21)

Wrong dose 3 6

Interacting medication

2 2

Alcohol excess

3 0

Unknown 12 13

Vitamin K (n=20)

Warfarin omission (n=21)

1st follow up INR:

Mean 4.7 4.8

Range 2-16.6 1.6-18.6

No with INR>4.5 7 10

No with INR >8.0 2 2

No with INR<2.0 0 2

1st follow up INR

Warfarin omission

0

5

10

15

20

25

INR

Vitamin K

0

5

10

15

20

25

INR

Vitamin K Warfarin omission

Day 7 INR

Mean 2.7 2.4

Range 1.1-5.5 1.0-5.1

No with INR>4.5

3 2

No with INR<2.0

5 8

Clinical events

• One patient from each group admitted with bleeding complications

• One patient in warfarin omission group had a breakthrough PE

Conclusions

• After omitting warfarin in patients with an INR>8, 50% still had a raised INR after 3 days

• Oral vitamin K at a 2 mg dose achieved at least comparable results within 24 hours

• Both patient groups had unstable INR control for at least 1 week after the event

• Use of oral vitamin K was not associated with warfarin resistance